Last time the under 21s were in action at the Madejski Stadium in August 2001 Defoe, a second half substitute, netted a brace as England ran riot, defeating Holland 4-0.
However, FA spokesman Andrin Cooper confirmed that David Platt will be without Defoe on Friday and maybe next Tuesday as well.
"Jermain will not travel out for Friday's game. He is going to stay at home and work with medical staff at his club. However, we are quietly confident that he will be available for Tuesday's match against Macedonia at Reading," he said, speaking to TheFA.com.
Defoe shot to fame two years ago when as a teenager he netted thirty times in one season on loan at Second Division Bournemouth. In that time he went on an incredible run to win himself a place in the record books, scoring in twelve consecutive games.